DESCRIPTION (applicant's abstract): The overall goal of this proposal is to determine whether BY55 (a novel cell surface marker) can serve as a means to define the differentiative pathway, potency, and expansion potential of CD8+ T cell subsets. Vigorous CD8 CTL and CD4 T helper responses are associated with the control of HIV replication. Lymphocyte cell surface markers that would distinguish cytolytic effector from precursor CTL would be of great value in measuring cytolytic effector activity and might provide a new means to clinically assess the potency and expansion of potential of CTL. A monoclonal Ab, BY55, has been identified by this group, which binds to all lymphocytes with cytolytic effector activity. In HIV infected individuals, the level of CD8+BY55+ T cells is increased, suggesting a role for BY55+ CTL in the response to HIV. The researchers have cloned the gene encoding BY55. The cDNA sequence predicts a (glgycoslyphosphatidylinostiol)gpi-anchored protein with a single Ig-like domain with homology to killer inhibitory receptors. BY55 was expressed on all intestinal IELs. The investigators have shown that the peripheral blood CD8+CD28- and CD8+BY55+ T cell subsets are virtually identical and it is known that the CD8+CD28+ precursor CTL may receive a B7 co-stimulatory signal and terminally differentiate into CD8+CD28-BY55+ effector CTL and that some of the peripheral blood CD8+CD28- subset may represent recirculation from mucosal epithelial sites. CD8+BY55+ T cells may represent a population with limited expansion possibilities. The specific aims of this proposal are: #1 to test the hypothesis that cytotoxic effector lymphocytes develop from CD8+CD28+B55- precursors into CD8+CD28-BY55+ effector cells. #2 To determine if BY55 is required for the development of anti-SIV CTL and determine the location of BY55+ CTL in vivo and in SIV infected rhesus macaques and in normal and HIV infected humans. #3 To characterize BY55 counter receptor expression and molecular identify using BY55-Ig fusion protein, and to determine the function of BY55 in the development of CTL using recombinant BY55-Ig fusion protein and new anti BY55 mAbs.